The human immunodeficiency virus type 1 (HIV-1) is an emergent virus of great public health significance. The continual evolution of HIV-1 into groups (M, N and O) and, further, into clades has had a tremendous impact on both the efficacy of antiviral therapeutics and the design of HIV/AIDS vaccines. HIV-1 group M viruses are organized genotypically into subtypes or clades alphanumerically designated A through K, with HIV-1 clades A and C accounting for the overwhelming burden of HIV disease globally. While HIV-1 clade C viruses predominate in the Southern and Eastern regions of Africa, throughout India and China, subtype A viruses are primarily found in Western and Central Africa, Central Europe and Thailand. The NIH Vaccine Research Center (VRC) is dedicated to developing HIV/AIDS vaccines that will elicit effective cellular immune responses against HIV-1 clades A, B and C. However, without the guidance of correlates of effective antiviral immunity, either natural or vaccine induced, developing effective vaccines is severely hampered. Accordingly, it is critical that we further our understanding of antiviral cellular immune responses in HIV-1 nonB clade infections, and underlying determinants of nonB clade viral fitness. To address these issues, the HIV section of the Viral Pathogenesis Laboratory (VPL) will examine antiviral cellular immunity in HIV infected African and African immigrant cohorts utilizing intracellular cytokine staining (ICS) FACS-based assays. Cross-clade immunity will be assessed by using peptide pools representing HIV-1 clades A, B and C. In addition, we will pursue studies to examine primary HIV-1 subtype C and A isolates in vitro according to cytopathicity, viral entry characteristics and resistance to antiviral properties of various entry and fusion based inhibitors